Researchers from the global health system Cleveland Clinic recently published a study that shows why women are more at risk of Alzheimer’s disease. The researchers analyzed the genes and brain tissue of patients with Alzheimer’s. They found that differences in brain immunometabolism – the interactions between the immune system and the ways cells create energy – may contribute to women’s increased risk for the disease and its severity.
Summary of the research findings on women and Alzheimer’s
The findings, published in the journal Alzheimer’s and Dementia, offer important insight into developing sex-specific treatment and prevention options for Alzheimer’s disease. According to Alzheimer’s Disease International, there were over 55 million people worldwide living with dementia in 2020, with the number expected to almost double every 20 years.
“Our immune systems depend on communication between different cell types in our bodies, which are fueled by energy created from unique metabolic processes,” said Justin Lathia, Ph.D. and vice chair of the Department of Cardiovascular and Metabolic Sciences. Dr Lathia is the co-author on the paper.
“As sex influences both the immune system and metabolic process, our study aimed to identify how all of these individual factors influence one another to contribute to Alzheimer’s disease.”
Staff Photograph taken in Studio
A Gene Expression for Alzheimer’s
The research is a collaboration between researchers at the Lerner Research Institute and physicians at the Lou Ruvo Center for Brain Health in Ohio and Nevada. The team analyzed brain samples and publicly available sequencing data obtained from 469 Alzheimer’s patients.
They looked for changes in gene expression between males and females in immune function, cellular metabolism, and communication between brain cells. They found sex-specific differences in all three areas, with the notable difference in microglia – immune cells in the brain.
What they found in women versus men
Changes in microglia were greater in the brains of female patients compared to males.
“Women are more likely to develop Alzheimer’s disease, and experience faster cognitive decline compared to their male counterparts. These differences between the sexes should be accounted for when designing medications and conducting clinical trials,” said Feixiong Cheng, Ph.D., Associate Staff, Genomic Medicine Institute and lead author of the paper. “These findings build on our knowledge of each part of the systems that play into Alzheimer’s and are critical to determining appropriate treatments.”
Women’s Alzheimer’s Movement
The study is part of an ongoing effort between the Cleveland Clinic and the Women’s Alzheimer’s Movement (WAM) to further understand the link between sex and all neurodegenerative conditions.
“At its core Alzheimer’s disease is a woman’s health issue. To address it, we must understand how biological sex contributes to the underpinnings of this disease,” said Jessica Caldwell, Ph.D., director of the WAM Prevention Center at Cleveland Clinic and another co-author of the paper.
“These findings confirm that we need to look at sex differences in the way the body and brain systems communicate to be able to truly offer women personalized care and we look forward to continuing this research.”
Notes on the study
The study was funded in part by a grant from the National Institutes of Health (R01AG084250) that supports the use of system biology and multi-omics approaches to untangle the complex interactions between our immune systems, inflammation, and sex-based differences in Alzheimer’s disease.
Recently, Dr. Cheng has been awarded $6.3 million from the NIH to support sex-based research in Alzheimer’s disease. Along with Dr. Lathia, their project, “Microglial Activation and Inflammatory Endophenotypes Underlying Sex Differences of Alzheimer’s Disease” aims to identify novel peripheral-central neuroimmune mechanisms to better understand sex differences in Alzheimer’s.
In addition, Drs. Cheng and Caldwell were awarded $4 million from the National Institutes of Neurological Disorders and Stroke of the NIH to further examine the role of the microbiome-gut-brain axis in Alzheimer’s disease. Their project, “Dark GPCR Signaling Underlying the Microbiome Gut Brain Axis for Alzheimer’s Disease and Related Dementia” aims to characterize protein receptors in the gut to determine if they offer potential prevention and treatment strategies for Alzheimer’s disease and is supported by award #RF1NS133812.
